Prostate Cancer最新文献

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2 (∗)1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23-3.18) for unselected cases and 3.39 (1.78-6.47) for familial cases, indicating that CHEK2 (∗)1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2(∗)1100delC should be considered in men with a familial history of prostate cancer.

Objectives. The aims of this study were to compare the outcomes of robotic assisted laparoscopic prostatectomy (RALP) between patients who had larger (≥75 g) and smaller (<75 g) prostates and to evaluate the performance of PSA density (PSAD) in determining the oncological outcome of surgery. Methods and Materials. 344 patients who underwent RALP at a single institution were included in the study. Preoperative risk factors and postoperative, oncological outcomes, erectile function, and continence status were recorded prospectively. Results. During a mean follow-up of 20 months, biochemical recurrence (PSA > 0.2) was observed in 15 patients (4.3%). Prostate size ≥75 g was associated with lower Gleason score on final pathology (P = 0.004) and lower pathological stage (P = 0.02) but an increased length of hospital stay (P = 0.05). PSAD on binary logistic regression independently predicted biochemical recurrence (BCR) when defined as postoperative PSA >0.1 (P = 0.001) and PSA >0.2 (P = 0.039). In both instances PSA was no longer a significant independent predictor. Conclusions. RALP in large prostates (≥75 g, <150 g) is as safe as RALP in smaller prostates and is associated with a lower pathological grade and stage. Higher PSAD is independently associated with BCR and is superior to PSA as a predictor of BCR after RALP.

Background. Prior studies evaluating the effect of statins or acetylsalicylic acid (ASA) on the survival of men receiving prostate cancer were treatment have reported conflicting results, and have not adjusted for comorbidity. Our aim is to investigate the influence of statins and ASA on prostate cancer survival, when comorbidity is adjusted for, in men treated with external beam radiation therapy (EBRT) for prostate cancer. Methods. A cohort of 3851 patients with prostate cancer treated with curative EBRT ± androgen deprivation therapy (ADT) between 2000 and 2007. Stage, treatment, medication use, and Charlson comorbidity index (CCI) scores were analyzed. Results. Median followup was 8.4 years. Mean age was 70.3 years. Neoadjuvant ADT was used in 67%. Statins were used in 23%, ASA in 24%, and both in 11%. Comorbidity scores were 0 in 65%, 1 in 25%, and ≥2 in 10% of patients. Statin and ASA use were associated with increased age and comorbidity. Although statin and ASA use were significantly associated with improved prostate cancer specific survival (PCSS) on univariate analysis, neither were on multivariate analysis. Conclusion. Neither statin nor ASA use impacted PCSS on multivariate competing risks analysis. Survival was impacted by increased comorbidity as well as statin and ASA use.

Background and Purpose. Life expectancy data could identify men with favorable post-radiation prostate-specific antigen (PSA) failure kinetics unlikely to require androgen deprivation therapy (ADT). Materials and Methods. Of 206 men with unfavorable-risk prostate cancer in a randomized trial of radiation versus radiation and ADT, 53 experienced a PSA failure and were followed without salvage ADT. Comorbidity, age and established prognostic factors were assessed for relationship to death using Cox regression analyses. Results. The median age at failure, interval to PSA failure, and PSA doubling time were 76.6 years (interquartile range [IQR]: 71.8-79.3), 49.1 months (IQR: 37.7-87.4), and 25 months (IQR: 13.1-42.8), respectively. After a median follow up of 4.0 years following PSA failure, 45% of men had died, none from prostate cancer and no one had developed metastases. Both increasing age at PSA failure (HR: 1.14; 95% CI: 1.03-1.25; P = 0.008) and the presence of moderate to severe comorbidity (HR: 12.5; 95% CI: 3.81-41.0; P < 0.001) were significantly associated with an increased risk of death. Conclusions. Men over the age of 76 with significant comorbidity and a PSA doubling time >2 years following post-radiation PSA failure appear to be good candidates for observation without ADT intervention.

Background. Increasing body mass index (BMI) is associated with increased risk of mortality; however, quantifying weight gain in men undergoing androgen deprivation therapy (ADT) for prostate cancer (PC) remains unexplored. Methods. Between 1995 and 2001, 206 men were enrolled in a randomized trial evaluating the survival difference of adding 6 months of ADT to radiation therapy (RT). BMI measurements were available in 171 men comprising the study cohort. The primary endpoint was weight gain of ≥10 lbs by 6-month followup. Logistic regression analysis was performed to assess whether baseline BMI or treatment received was associated with this endpoint adjusting for known prognostic factors. Results. By the 6-month followup, 12 men gained ≥10 lbs, of which 10 (83%) received RT + ADT and, of these, 7 (70%) were obese at randomization. Men treated with RT as compared to RT + ADT were less likely to gain ≥10 lbs (adjusted odds ratio (AOR): 0.18 [95% CI: 0.04-0.89]; P = 0.04), whereas this risk increased with increasing BMI (AOR: 1.15 [95% CI: 1.01-1.31]; P = 0.04). Conclusions. Consideration should be given to avoid ADT in obese men with low- or favorable-intermediate risk PC where improved cancer control has not been observed, but shortened life expectancy from weight gain is expected.

Purpose. Increasing body mass index (BMI) is associated with higher risk prostate cancer (PC) at presentation. Whether increasing BMI also prompts earlier salvage androgen suppression therapy (sAST) is unknown. Materials and Methods. Between 1995 and 2001, 206 men with unfavorable risk PC were treated with radiation therapy (RT) or RT and six months of androgen suppression therapy in a randomized controlled trial (RCT). 108 sustained PSA failure; 51 received sAST for PSA approaching 10 ng/mL; 49 with BMI data comprised the study cohort. A multivariable Cox regression analysis identified pretreatment factors associated with earlier sAST receipt. Results. Increasing BMI prompted earlier sAST (median years: 3.7 for overweight/obese, 6.9 for normal weight; adjusted hazard ratio (AHR): 1.11; 95% CI: 1.04, 1.18; P = 0.002) as did high versus other risk PC (median: 3.2 versus 5.2 years; AHR: 2.01; 95% CI: 1.05, 3.83; P = 0.03). Increasing median time to sAST was observed for overweight/obese men with high versus other risk PC and for normal-weight men with any risk PC being 2.3, 4.6, and 6.9 years, respectively (P < 0.001 for trend). Conclusion. Increasing BMI was associated with earlier sAST. A RCT evaluating whether BMI reduction delays or eliminates need for sAST is warranted.

Aim. To compare the diagnostic performance of diffusion weighted imaging (DWI) using b-values of 1000 s/mm(2) and 2000 s/mm(2) at 3 Tesla (T) for the evaluation of clinically significant prostate cancer. Matherials and Methods. Seventy-eight prostate cancer patients underwent a 3T MRI scan followed by radical prostatectomy. DWI was performed using b-values of 0, 1000, and 2000 s/mm(2) and qualitatively analysed by two radiologists. ADC maps were obtained at b-values of 1000 and 2000 s/mm(2) and quantitatively analyzed in consensus. Results. For diagnosis of 78 prostate cancers the accuracy of DWI for the young reader was significantly greater at b = 2000 s/mm(2) for the peripheral zone (PZ) but not for the transitional zone (TZ). For the experienced reader, DWI did not show significant differences in accuracy between b-values of 1000 and 2000 s/mm(2). The quantitative analysis in the PZ and TZ was substantially superimposable between the two b-values, albeit with a higher accuracy with a b-value of 2000 s/mm(2). Conclusions. With a b-value of 2000 s/mm(2) at 3T both readers differentiated clinical significant cancer from benign tissue; higher b-values can be helpful for the less experienced readers.

Background. Molecular markers for prostate cancer (PCa) risks are currently lacking. Here we address the potential association of a dinucleotide polymorphism (DNP) in exon 2 of the p73 gene with PCa risk/progression and discern any disruption of p73 protein isoforms levels in cells harboring a p73 DNP allele. Methods. We investigated the association between p73 DNP genotype and PCa risk/aggressiveness and survival by fitting logistic regression models in 1,292 incident cases and 682 controls. Results. Although we detected no association between p73 DNP and PCa risk, a significant inverse relationship between p73 DNP and PCa aggressiveness (AT/AT + GC/AT versus GC/GC, OR = 0.55, 95%Cl = 0.31-0.99) was detected. Also, p73 DNP is marginally associated with overall death (dominant model, HR = 0.76, 95%Cl = 0.57-1.00, P = 0.053) as well as PCa specific death (HR = 0.69, 95%Cl = 0.45-1.06, P = 0.09). Western blot analyses for p73 protein isoforms indicate that cells heterozygous for the p73 DNP have lower levels of ∆Np73 relative to TAp73 (P < 0.001). Conclusions. Our findings are consistent with an association between p73 DNP and low risk for PCa aggressiveness by increasing the expressed TAp73/∆Np73 protein isoform ratio.

Purpose. We investigated whether NS-RP increased risk of PSA failure and whether PSA should be included as a selection criterion for NS. Methods. We evaluated 357 consecutive men with screen-detected PC who underwent open RP without adjuvant radiotherapy between 9/11/2001 and 12/30/2008. Criteria for NS included Gleason score ≤3 + 4, percentage of positive biopsies (PPB) ≤50%, percentage of core involvement ≤50%, nonapical location, no perineural invasion, and no palpable disease on pre- or intraoperative exam but did not include a PSA threshold. Cox multivariable regression assessed whether increasing PSA or unilateral- or bilateral-NS versus non-NS-RP was associated with PSA failure adjusting for prognostic factors. Results. After a median follow-up of 3.96 years, 34 men sustained PSA failure (9.5%). Increasing PSA was significantly associated with increased risk of PSA failure in the interaction model (adjusted hazard ratio (AHR): 1.09 [95% CI: 1.03-1.16]; P = 0.005), whereas unilateral (AHR: 1.24 [95% CI: 0.36-4.34]; P = 0.73) or bilateral NS (AHR: 0.41 [95% CI: 0.06-2.59]; P = 0.34) versus non-NS RP was not. Conclusion. NS-RP in a screened cohort did not increase risk of PSA failure using NS criteria not including PSA.

Prostate cancer is the most frequently diagnosed cancer in men and often requires surgery. Use of near infrared (NIR) technologies to perform image-guided surgery may improve accurate delineation of tumor margins. To facilitate preclinical testing of such outcomes, here we developed and characterized a PSMA-targeted small molecule, YC-27. IRDye 800CW was conjugated to YC-27 or an anti-PSMA antibody used for reference. Human 22Rv1, PC3M-LN4, and/or LNCaP prostate tumor cells were exposed to the labeled compounds. In vivo targeting and clearance properties were determined in tumor-bearing mice. Organs and tumors were excised and imaged to assess probe localization. YC-27 exhibited a dose dependent increase in signal upon binding. Binding specificity and internalization were visualized by microscopy. In vitro and in vivo blocking studies confirmed YC-27 specificity. In vivo, YC-27 showed good tumor delineation and tissue contrast at doses as low as 0.25 nmole. YC-27 was cleared via the kidneys but bound the proximal tubules of the renal cortex and epididymis. Since PSMA is also broadly expressed on the neovasculature of most tumors, we expect YC-27 will have clinical utility for image-guided surgery and tumor resections.